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Trial of treatments for vCJD to launch

Eighteen years after BSE first emerged in the UK, we still have little idea how to treat people who have contracted the human version, variant Creutzfeldt-Jakob Disease (vCJD).

An investigation by New Scientist has revealed that the relatives of people with vCJD are frustrated by the slow progress being made to find new treatments. Time and effort are being wasted researching drugs that simply do not work, they say, while other, radical, treatments are not being made readily available.

But while researchers privately disagree over which approaches show most promise, they say there is now a united effort to find a drug best able to save lives.

Later this month, the UK government’s Medical Research Council will officially launch a trial of potential treatments, after four years of argument over which to test.

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Called the “PRION-1” trial it will focus on quinacrine, an anti-malarial drug that showed early promise in treating various forms of CJD. The National Prion Disease Clinic at St Mary’s Hospital in London has already given the drug to around 20 patients, but the results are not yet in.

Liver complications

Quinacrine first came to prominence in 2001, when Nobel prizewinner Stanley Prusiner of the University of California at San Francisco used it to treat Rachel Forber, a Briton who contracted vCJD.

Forber’s condition initially improved, but she died, apparently from liver complications triggered by the drug. Prusiner’s team is now trying to improve quinacrine’s efficacy while limiting its side effects. The researchers say that by fusing two quinacrine molecules together they have made the drug 10 times more effective in laboratory tests.

But others think quinacrine is unreliable. Markus Otto leads a team at the University of Göttingen in Germany that has been investigating treatments for CJD since 1996, when the variant form of the disease was discovered. He says that patients given quinacrine develop yellow skin, vomit and have dangerously high levels of toxic liver enzymes. “With quinacrine, we only saw side effects, so we won’t use it.”

Don Simms, the father of Belfast vCJD patient Jonathan Simms, agrees that quinacrine has few benefits. “To put quinacrine in a trial is a waste of public money. In its current form it doesn’t work,” he says.

Special report&colon; New Scientist print edition presents a 10-page special on the spread of BSE to North America and beyond, on sale from Thursday 5th August.

Simms would rather see the PRION-1 trial test another drug called pentosan polysulphate (PPS), which is used to treat infections of the urinary tract. When infused directly into the brains of CJD patients, PPS appears to stop abnormal prion proteins from forming clumps and killing neurons.

Jonathan Simms was the first to be given the drug in January 2003, and is still alive 18 months later, even though at one point before his treatment began he had been given just hours to live.

“He’s not got better, but he has remained stable, and I believe that in the absence of anything else PPS should be tried,” Don Simms told New Scientist.

At least eight surviving patients have received PPS. Although the law in England and Wales prevents the media reporting details of individual cases, New Scientist understands that four of the recipients have vCJD, one has sporadic CJD (the most common form), and three have an inherited form of CJD called Gerstmann-Sträussler-Scheinker syndrome.

At least three of the patients have been treated with PPS at the National CJD Surveillance Unit in Edinburgh. “This is not because we think intraventricular PPS is a good treatment or should be done,” says Richard Knight, consultant neurologist at the unit. “But we recognise that some individuals insist on this treatment, and if they want it, we think it’s unreasonable not to offer it.”

Early promise

He backs the position of the UK government’s Committee on Safety of Medicines, which says that PPS may halt or delay the progress of CJD, but should not be given to patients in the latter stages of the disease as it prolongs life without improving health.

Don Simms agrees that his son has shown little signs of genuine recovery, but says that he has improved in some ways. “Jonathan’s suffered no adverse side effects, his blood pressure and his pulse are back to normal, and he’s able now to clear his own airway and swallow his own saliva. I don’t think it’s a cure, but it has slowed down or stopped the disease.”

But Simms says that, despite the drug’s early promise, it is not readily available. In England and Wales, for instance, relatives of CJD patients who cannot decide for themselves must ask the courts to sanction the treatment.

Otto says he would like to prescribe PPS to people with CJD and has found a neurosurgeon willing to administer it. But ethical review boards and insurers have reservations over the treatment and have not yet given it the go-ahead.

An MRC spokeswoman says that the PRION-1 trial will monitor patients given PPS, although it will not officially test the drug. And the trial has been designed so that new treatments can be evaluated as and when they emerge.

One of those could be flupirtine, a painkiller being investigated by Otto’s team. In a clinical trial it appeared to slow the decline in mental sharpness in CJD patients compared with those given a placebo. But, like PPS, it could not reverse the disease or stop it progressing. As a result, Otto’s team is treating patients who are still only mildly affected by the disease.